By Mariya Rosenblit, MD
Peer Reviewed
On Friday, the Greek parliament and Eurozone finance ministers approved an international loan deal, saving the Greek government from going into default on their debts. The package is 86 billion euros and requires Greece to put in place spending limits, new tax increases, and raising the retirement age. This allows Greece to remain in the Eurozone and make its 3.2 billion euro payment to the European Central bank on August 20th. The hope is that the bailout will allow Greece to emerge from its recession and show economic growth by 2018. A portion of the Greek parliament is against the austerity terms in the loan deal, and a political group called the Left Platform is forming an antibailout movement. Agreeing to the deal has undermined support for the Greek prime minister, Mr. Alexis Tsipras [1]. A vote of confidence in the Greek government, followed by new elections may occur soon after August 20th.
This week in medical news:
Does testosterone supplementation increase atherosclerosis progression?
Low testosterone is a common and recognized condition among older men. The long term effects of supplemental testosterone remain unclear. Studies to date have provided mixed results, with some associating low testosterone with increased risk of cardiovascular disease, dyslipidemia, and metabolic syndrome. On the other hand, a recently conducted trial was stopped early because increased rates of adverse cardiovascular events in patients receiving testosterone supplementation [2].
To better address the effects of testosterone supplementation on cardiovascular risk, Basaria, et al. conducted a randomized double blind placebo controlled trial [3]. The trial enrolled 308 men 60+ years old with low free testosterone levels, randomizing them to testosterone supplementation vs placebo for 3 years. The primary outcome was progression in coronary artery calcium score and carotid artery intima-media thickness, two markers of atherosclerosis. There was no significant association between testosterone supplementation and changes in intima-media thickness or coronary artery calcium score changes. Interestingly, there were also no differences in lipid profiles, sexual function, or quality of life ratings between the two groups.
This trial suggests that testosterone supplementation does not hasten atherosclerosis progression and may be safe. A limitation of the study is that its outcomes were markers of atherosclerosis and not adverse cardiovascular events. Therefore it cannot definitively be said from this study that testosterone supplementation is safe and does not incur increased cardiovascular risk.
Can HLA-DPB1 expression predict the risk of graft-versus-host disease?
Graft-versus-host-disease (GVHD) is a serious complication of hematopoietic cell transplant. Mismatches in HLA types results in a higher risk of GVHD. The contribution of specific HLA mismatches remains uncertain, especially HLA-DPB1. There have been mixed results in terms of outcomes with HLA-DPB1 matches and mismatches [4]. Two variants in the regulatory region of the HLA-DPB1 allele result in different levels of expression of HLA-DPB1 on the cell surface. In a retrospective study, Petersdorf et al. [5] looked at the effect of HLA-DPB1 expression on rates of acute GVHD in patients with HLA-DPB1 mismatch. The study found that recipients with the low expression DPB1 allele, who received a HLA-DPB1 mismatched transplant from a donor with the high expression allele, had a higher risk of acute GVHD compared to low expression allele recipients receiving mismatched transplant from a low expression allele donor (HR 1.54, 95% CI 1.25-1.89, P <0.001).
This study shows the level of cell surface expression of HLA-DPB1 influences the risk of HLA-DPB1 mismatches, explaining the variability in risk seen among HLA-DPB1 mismatches. On a broader level, this study suggests that donor-recipient matching for hematopoietic cell transplantation should extend beyond structural analysis to functional analysis in order to better match patients. The question becomes not only if the cell surface protein has a different molecular structure, but also to what extent this protein is being expressed on the cell surface. In the future, screening for HLA matching may extend to transcriptional and posttranscriptional regulation of gene expression.
Can Coronary CTA be used to assess the need for catheterization instead of nuclear myocardial perfusion imaging?
Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). Its use does not come without drawbacks, including procedural complications, radiation exposure, and resource utilization. Frequently non-invasive imaging techniques are used to select patients with acute chest pain for coronary angiography. The ideal imaging modality is not known. A newer imaging technique, coronary computed tomography angiography (CCTA) provides an enticing option compared to myocardial perfusion imaging (MPI) because of lower radiation doses and possible decreased resource utilization. In a prospective randomized trial, Levsky, et al. [6] assessed whether CCTA or MPI is better at predicting the need for coronary angiography in patients with acute chest pain. Patients without history of CAD admitted to telemetry for unstable angina were randomized to either receive CCTA or MPI and then followed for one year. The primary outcome was rate of coronary angiography without revascularization. No significant difference in the primary outcome was found between the two groups, HR 0.77, (P = 0.44).
According to this study, CCTA and MPI are equally effective in detecting those with acute chest pain who do not have clinically significant obstructive CAD. Since CCTA has a significantly lower dose of radiation (9.6 vs 27 mSv), this is a promising finding that encourages wider use of CCTA. Larger, multi-center trials with longer follow-up are needed to confirm this data. In the future, CCTA may become a more ubiquitous test in risk assessing patients with unstable angina.
Elotuzumab decreases disease progression in multiple myeloma
Despite improvements in treatment, multiple myeloma still has a median survival of 5 years. Current outcomes are limited by relapse and the development of drug resistance. Currently, lenalidomide and dexamethasone is the standard regimen for patients with relapsed or refractory disease.
A phase 3 randomized trial [7] evaluated the effect of the addition of elotuzumab to the standard therapy in 646 patients with relapsed or refractory multiple myeloma, defined as disease progression despite treatment with one of 3 first line regiments. Elotuzumab is a monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7), a protein that is expressed only on myeloma and natural killer cells. Elotuzumab directly activates natural killer cells to destroy multiple myeloma cells and also binds to multiple myeloma cells activating antibody-dependent cell mediated cytotoxicity. The studies co-primary endpoints were progression-free survival and the overall response rate.
The addition of elotuzumab significantly improved median progression-free survival, 19.4 months versus 14.9 months in the control group (HR 0.70, P<0.001). Overall response rates to treatment were higher in the elotuzumab group, 79% vs. 66% in the control group for an odds ratio of 1.9 (P<0.001). This indicates double the chance of treatment response with an Elotuzumab containing regimen. Adverse events were similar between the two groups and there were no differences between pain severity or quality of life ratings. This is an exciting new therapy option for multiple myeloma patients providing increased survival via activation of the innate immune system.
Quick-Cuts
An opinion piece published in JAMA on the contribution of racial bias to health care disparities [8].
A commentary in the NEJM on whether there is such a thing as too much information in physician communication [9].
A pilot study showing that colchicine may reduce infarct size in STEMI patients treated with PCI[10].
Dr. Mariya Rosenblit is a 1st year resident at NYU Langone Medical Center
Peer reviewed by Ian Henderson, MD, 2nd year resident, NYU Langone Medical Center
Image courtesy of Wikimedia Commons
References
1) Alderman L and Kitsantonis N. As Greek Bailout Deal Passes, Alexis Tsipras Faces Rebellion. NY Times Aug 14, 2015. http://www.nytimes.com/2015/08/15/world/europe/greece-bailout-vote.html?_r=0
2) Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109-122 http://www.nejm.org/doi/full/10.1056/NEJMoa1000485
3) Basaria S, Harman SM, Travison TG, et al. Effects of testosterone administration on subclinical atherosclerosis progression in order men with low or low-normal testosterone levels. JAMA 2015;314(6):570-581. http://jama.jamanetwork.com/article.aspx?articleid=2425744
4) Shaw BE, Mayor NP, Russell NH, et al. Diverging effects of HLA-DPB1 matching status on outcome following unrelated donor transplantation depending on disease stage and the degree of matching for other HLA alleles. Leukemia2010;24:58-65. http://www.nature.com/leu/journal/v24/n1/full/leu2009239a.html
5) Petersdorf EW, Malkki M, O’hUigin C, et al. High HLA-DP Expression and Graft-versus-Host Disease. N Engl J Med 2015;373:599-609. http://www.nejm.org/doi/full/10.1056/NEJMoa1500140#t=article
6) Levsky JM, Spevack DM, Travin MI, et al. Coronary Computed Tomography Angiography Versus Radionuclide Myocardial Perfusion Imaging in Patients with Chest Pain Admitted to Telemetry. Ann Intern Med 2015;163:174-183. http://annals.org/article.aspx?articleid=2301406
7) Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med 2015;373:621-631. http://www.nejm.org/doi/full/10.1056/NEJMoa1505654#t=article
8) Williams, David and Wyatt Ronald. Racial Bias in Health Care and Health. JAMA 2015;314(6):555-556. [http://jama.jamanetwork.com/article.aspx?articleid=2425753]
9) Rosenbaum L. The Paternalism Prefrence – Choosing Unshared Decision Making. N Engl J Med 2015;373:589-592 http://www.nejm.org/doi/full/10.1056/NEJMp1508418?query=featured_home
10) Deftereos S, Giannopoulos G, Angelidis C. Anti-inflammatory treatment with colchicine in acute myocardial infection: A Pilot Study. Circulation Aug 11, 2015 http://circ.ahajournals.org/content/early/2015/08/11/CIRCULATIONAHA.115.017611.abstract